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PubMed This is a summary of 17 peer-reviewed journal articles Updated
Pediatrics

How NBS Affects Growth and the Immune System

At a Glance

Nijmegen breakage syndrome can affect a child’s head size, physical growth, development, and immune defenses, leading to recurrent infections in some children. Girls may also develop ovarian problems, so regular growth, immune, developmental, and hormone monitoring helps guide individualized care.

Nijmegen Breakage Syndrome (NBS) affects how a child’s body grows, develops, and protects itself from germs. Because the DNA repair system is not working correctly, cells throughout the body—especially in the brain and the immune system—face unique challenges. While every child’s experience is different, understanding these common physical and biological patterns can help you and your care team stay proactive [1][2].

Physical Features and Growth

One of the most recognizable signs of NBS is a smaller-than-average head size, known as microcephaly [1]. For most children (about 80%), this is present at birth or noticed shortly after [2]. As the child gets older, the microcephaly often becomes more noticeable because the head grows more slowly than the rest of the body [1][3].

Many children with NBS also share a characteristic facial appearance [4]. This usually includes a prominent nose, a sloping forehead, and a somewhat smaller jaw [4][1]. Physical growth is also typically slower than average, leading to a smaller stature (mild growth retardation) throughout childhood [5][1].

Development and Learning

Children with NBS may experience developmental delays, learning differences, or mild to moderate intellectual disability [1][6]. This may mean your child takes a little longer to reach certain milestones, like speaking or mastering complex tasks. While some adults with NBS have shown more significant cognitive challenges, it is important to remember that every child’s potential is unique and shaped by the support and early intervention they receive [1][7].

The Immune System: A Complex Shield

The immune system in NBS is often described as having a combined immunodeficiency [8]. This means both the “specialized soldiers” (T-cells) and the “antibody factories” (B-cells) may not work as they should [9][10].

  • Cellular Defect (T-cells): Children often have lower numbers of T-cells, which are crucial for fighting viruses and coordinating the immune response [11][12].
  • Humoral Defect (B-cells and Antibodies): The body may struggle to produce enough antibodies (like IgG or IgA) to fight off bacteria [5][8]. This can also mean that standard childhood vaccines might not provide the full level of protection they do for other children [13][8].

Clinically, this often shows up as frequent or “recurrent” infections, particularly in the sinuses, ears, or lungs (sinopulmonary infections) [2][5]. Interestingly, the laboratory numbers don’t always match how sick a child feels—some children have very low immune counts but stay relatively healthy, while others with better-looking numbers may get sick more often [2][8].

Granulomas and Inflammation

Sometimes, the immune system in NBS doesn’t just “under-react” to germs; it can also “over-react” or become confused. This can lead to granulomas—small clusters of inflamed tissue that can appear on the skin or inside organs like the lungs [2][14]. These are an inflammatory response. Crucially, a specialist must thoroughly evaluate any suspected granuloma (often through cultures or a biopsy) to rule out an active infection before treating the inflammation with immunosuppressants like steroids [14][15].

Endocrine and Reproductive Health in Females

For girls and women with NBS, the genetic change in the NBN gene affects how the ovaries develop and function. This often leads to a condition called premature ovarian insufficiency (POI) or hypergonadotropic hypogonadism [16][1].

In simple terms, the ovaries may not produce the typical levels of hormones (like estrogen) or release eggs as expected [4]. This can affect the timing or progression of puberty and often leads to infertility [4][3]. Early consultation with a pediatric endocrinologist is essential to monitor these hormone levels and discuss options for hormone replacement therapy to support bone health and overall development [4][16].

While these challenges are significant, knowing about them early allows you and your medical team to create a specialized monitoring plan that is tailored to your child’s specific needs [17][2].

Common questions in this guide

How can Nijmegen breakage syndrome affect a child’s growth and head size?
Nijmegen breakage syndrome often causes microcephaly, meaning a smaller head size, which may be present at birth or become more noticeable as head growth slows. Children may also grow more slowly overall and have a shorter stature. The pattern and severity vary, so clinicians track head circumference, height, and weight over time.
Why do children with NBS get repeated infections?
NBS can cause combined immune deficiency, meaning both T cells and antibody-producing B cells may be reduced or work less effectively. This can increase the risk of repeated ear, sinus, or lung infections and may reduce the protection provided by some routine vaccines. Immune test results do not always predict how often a child will become ill, so the care team considers both laboratory results and infection history.
What should we do if a child with NBS develops a possible granuloma?
A granuloma is a small area of inflamed tissue that can occur in the skin or organs such as the lungs. A specialist should evaluate it with appropriate testing, which may include cultures or a biopsy, to rule out an active infection. Immunosuppressive medicines such as steroids should not be started for suspected inflammation until infection has been carefully considered.
Can NBS affect puberty and fertility in girls?
Yes. Changes involving the NBN gene can lead to premature ovarian insufficiency, in which the ovaries do not make typical hormone levels or release eggs as expected. This may alter puberty and often causes infertility. A pediatric endocrinologist can monitor hormones and discuss hormone replacement therapy to support development and bone health.
Do children with NBS need developmental or school support?
Some children with NBS have developmental delays, learning differences, or mild to moderate intellectual disability, while others have fewer difficulties. Developmental assessment, early intervention, and individualized school accommodations can help match support to a child’s needs. Discuss speech, learning, and classroom support with the child’s care and school teams.
Should vaccine antibody levels be checked in a child with NBS?
The immune changes in NBS can mean that routine vaccines do not produce the same level of protection as they do in other children. The care team may consider checking vaccine-specific antibody levels along with T-cell, B-cell, and other immune results. An immunology specialist should guide vaccine and infection-prevention decisions for the individual child.

Questions to Ask Your Doctor

Curated prompts to bring to your next appointment.

  1. 1.What is our child's current head circumference percentile, and how do you expect this to change as they grow?
  2. 2.Based on our child's specific T-cell and B-cell counts, what is their level of infection risk right now?
  3. 3.Should we be checking our child's vaccine-specific antibody levels to see if their prior immunizations are providing protection?
  4. 4.If our child develops a persistent cough or skin bump that doesn't go away, how can we distinguish an infection from a granuloma?
  5. 5.For our daughter, at what age should we begin consulting with a pediatric endocrinologist to monitor her development and ovarian health?
  6. 6.What kind of developmental support or school accommodations do you typically recommend for children with NBS?

Questions For You

Tap a prompt to share your answer — we'll use it plus this page's context to start a tailored conversation.

References

References (17)
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    Nijmegen breakage syndrome: case report and review of literature.

    Hasbaoui BE, Elyajouri A, Abilkassem R, Agadr A

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    Prospective Study of a Cohort of Russian Nijmegen Breakage Syndrome Patients Demonstrating Predictive Value of Low Kappa-Deleting Recombination Excision Circle (KREC) Numbers and Beneficial Effect of Hematopoietic Stem Cell Transplantation (HSCT).

    Deripapa E, Balashov D, Rodina Y, et al.

    Frontiers in immunology 2017; (8()):807 doi:10.3389/fimmu.2017.00807.

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    DNA repair functional analyses of NBN hypomorphic variants associated with NBN-related infertility.

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    Human mutation 2020; (41(3)):608-618 doi:10.1002/humu.23955.

    PMID: 31729086
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    A case of premature ovarian insufficiency in Nijmegen breakage syndrome patient and review of literature. From gene mutation to clinical management.

    Szeliga A, Zysnarska A, Szklarska Z, et al.

    Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology 2019; (35(11)):999-1002 doi:10.1080/09513590.2019.1626366.

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    Nijmegen breakage syndrome: 25-year experience of diagnosis and treatment in Ukraine.

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    Derivation of homozygous Nijmegen breakage syndrome induced pluripotent stem cell line (MUNIi019-A).

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    Geographical Distribution, Incidence, Malignancies, and Outcome of 136 Eastern Slavic Patients With Nijmegen Breakage Syndrome and NBN Founder Variant c.657_661del5.

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    Circulating T Cells of Patients with Nijmegen Breakage Syndrome Show Signs of Senescence.

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    T Lymphocytes in Patients With Nijmegen Breakage Syndrome Demonstrate Features of Exhaustion and Senescence in Flow Cytometric Evaluation of Maturation Pathway.

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This page is for informational purposes only and does not constitute medical advice. Because Nijmegen breakage syndrome can affect growth, immunity, development, and ovarian function differently in each child, discuss monitoring and treatment with your child’s healthcare team.

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